E-mail: fuchs¦olimp.irb.hr
Summary: A series of new bis-(pyridinium, pyridinium-imidazolium and
imidazolium oximes) linked together with alkane, ether and diether
chains, with methyl, benzyl, phenyl and 4-fluorophenyl substituents at
position 3 of the imidazole ring, were tested. All compounds have been
characterized by elemental analysis, IR and NMR - spectroscopy. In vitro
inhibitory effect of the oximes (IC-50) was determined on human
erythrocyte AChE, and their acute toxicity (LD-50) determined in male
mice. From the preliminary investigations it was shown: the diether
linkage highers the inhibitory power in all classes of investigated
compounds. The bis-imidazolium oximes are stronger inhibitors than their
corresponding piridinium imidazolium analogues. In compounds containing
alkane chain, methyl and benzyle groups when compared to phenyl and
substituted phenyl groups strenghten the inhibitory power. The inhibitory
power (IC-50), reactivation of soman phosphylated AChE and protection of
human erythrocyte AChE against inhibition by soman were determined by
applying four new synthetized N-phenyl imidazolium oximes and several
pyridinium-quinuclidinium oximes. Acute toxicity (LD-50) in male mice was
determined "in vivo" as well as the protection against soman intoxication.

Research goals: It is well known that oximes are reactivators
ofacetylcholinesterases inhibited by organophosphorus compounds.Since this
property of oximes was observed, numerous compounds ofdifferent structure
have been synthetised and tested. The aim ofthis investigation is to test
antidotal properties of newsithetised imidazolium oximes against AChE
erythrocytes inhibitedby soman and other highly toxic
organophosphoruscompounds.Investigations are focused on the
biochemicalproperties of tested compounds responsible for antidotal
effects against highly toxic poisonings.Their
toxicity,reactivationpotency and protective ability against phosphylated
AChE will betested. Biological experiments of these new synthetised
oximeswill be done "in vivo" on the experimental animals as support
ofgiven "in vitro" results. The final goal of this project is to compare
the results of thedetermined activity of new synthetised imidazolium
oximes withactivities of usualy used antidotes (mono- and
bis-pyridiniumoximes) and to achieve better protection effects against
thesestrong poisons. The investigation was aimed at finding out to what
extent the nature of the p-CH3 substituent in N-phenyl imidazoline oximes
effects the "in vitro" inhibitory power (IC-50) on human erythrocyte AChE,
reactivation percentage of human erythrocyte AChE inhibited by soman and
"in vitro" protection against soman. Acute toxicity (LD-50) in male mice
was determined "in vivo" as well as the protection against soman
poisoning. In addition several compounds (quinuclidinium oximes) that
could have a possible reactivatory ability and their activity were
determined also.